Expression of nerve-regulated genes in muscles of mouse mutants affected by spinal muscular atrophies and muscular dystrophies

OBJECTIVE: Mature lobar transplantation will increase the pediatric donor organ pool, but it remains unknown whether such grafts will grow in a developing recipient and provide adequate long-term support. We hypothesized that a mature pulmonary lobar allograft implanted in an immature recipient would grow. METHODS: We investigated our hypothesis in a porcine orthotopic left lung transplant model using animals matched by the major histocompatibility complex to minimize the effects of chronic rejection. Twenty-three immature animals (< 12 weeks of age and < 10 kg total body weight) received either sham left thoracotomy (SH control, n = 4), left upper lobectomy to study compensatory growth (UL control, n = 4), age-matched immature whole left lung transplants (IWL TXP, n = 6), mature (donor > 1 yr in age and > 40 kg in total body weight) left lower lobe transplants (MLL TXP, n = 5), or mature left upper lobe transplants (MUL TXP, n = 4). Twelve weeks after implantation, functional residual capacity of the left lung was measured and arterial blood gas samples were obtained after the native right lung had been excluded. The graft was excised and weighed, and samples for microscopy and wet/dry ratios were collected. RESULTS: Initial and final graft weights were as follows: IWL TXP group (34.6 +/- 1.5 and 107.8 +/- 5.9 gm, p < 0.0001), MLL TXP group (72.4 +/- 6.8 and 111.4 +/- 8.7, p < 0.001), and MUL TXP group (32.8 +/- 1.3 and 92.8 +/- 7.1 gm, respectively, p < 0.004). No significant differences between groups were demonstrated when functional residual capacity, wet/dry ratios, or oxygenation were compared. Immunohistochemical staining for the nuclear antigen Ki-67 demonstrated dividing pneumocytes. CONCLUSIONS: We conclude that a mature lobar graft implanted into an immature recipient grows by pneumocyte division in this model. Mature lobar transplants can be expected to grow and provide adequate long-term function in developing recipients.     

Long-term effect of perfluorocarbon distension on the lung

BACKGROUND/PURPOSE: We have demonstrated previously that postnatal lung growth can be accelerated by continuous intrapulmonary distension with perfluorocarbon (PFC). The purpose of this study was to examine the effect of PFC distension on long-term lung function and to determine if shorter periods of lung distension would be sufficient to stimulate growth. METHODS: Eight neonatal lambs underwent a right thoracotomy. The superior segment of the right upper lobe of the experimental group (n = 5) was isolated and distended with PFC to an intrabronchial pressure of 7 to 10 mm Hg. The inferior segment was removed. After a 7-day distension period (the maximum period of exposure currently allowed for humans), the experimental animals underwent removal of the intrabronchial catheter and surgical closure of the bronchial stump. Control animals (n = 3) underwent right upper lobe inferior segmentectomy alone. Animals were allowed to breathe spontaneously and reach 3 to 6 months of age. Before death, all animals were evaluated by chest radiographs and ventilation-perfusion scans. Pulmonary venous blood gas levels were obtained. Lungs were harvested and airway fixed for morphometric analysis. RESULTS: Chest radiographs of the experimental group showed variable amounts of intrapleural and interstitial PFC but were otherwise normal. Results of ventilation/perfusion (VQ) scans of all experimental animals were normal. On retrieval, the right upper lobe of experimental animals appeared slightly hyperinflated compared with controls. Right upper lobe pulmonary vein PaO2 to left pulmonary vein PaO2 ratio was comparable in experimental and control animals (1.2 +/- .41 v 0.92 +/- .15). DNA to protein ratios were slightly higher in the right upper lobes of experimental animals, however, the difference was not statistically significant (.64 +/- .11 v .42 +/- .03). On histological evaluation, the airway epithelium and alveoli of the right upper lobe of experimental animals appeared normal. Lung morphometry results showed no statistically significant differences in alveolar number between experimental and control animals. CONCLUSIONS: From these preliminary data we conclude that (1) lung architecture is preserved in juvenile animals subjected to intrapulmonary PFC distension as neonates, (2) lung function is preserved in the lobar segment after PFC distension, and (3) intrapulmonary PFC distension appears to be safe at 3 to 6 months follow-up. However, 7 days of PFC distension is insufficient to promote lung growth.     

Pediatric lung transplantation. Indications, techniques, and early results

From July 1990 to April 1993, 36 lung transplantations in 33 patients were performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3 years). Eight children had been continuously supported with a ventilator for 3 days to 4.5 years before transplantation and three were supported by extracorporeal membrane oxygenation. Indications for lung transplantation in this pediatric population included the following: cystic fibrosis (n = 13), pulmonary hypertension, and associated congenital heart disease (n = 10), pulmonary atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3), pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1). Three children underwent retransplantation for acute graft failure (n = 2) or chronic rejection (n = 1). Pulmonary fibrosis was related to complications of treatment of acute of myelogenous leukemia with bone marrow transplantation in two children and to bronchiolitis obliterans, bronchopulmonary dysplasia, interstitial pneumonitis, and Langerhans cell histiocytosis in four others. Thirteen children underwent lung transplantation and concomitant cardiac repair. Bilateral lung transplantation, ventricular septal defect closure and pulmonary homograft reconstruction of the right ventricular outflow tract to the transplanted lungs was performed in three children by means of a new technique that avoids the need for combined heart-lung transplantation. Two patients had ventricular septal defect closure and single lung transplant for Eisenmenger's syndrome, two had ligation of a patent ductus arteriosus and transplantation, three additional children underwent atrial septal defect closure and lung transplantation, and two underwent lung transplantation for congenital pulmonary vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1-year survival 62%). Lung transplantation in children has been associated with acceptable early results, although modification of the adult implantation technique has been necessary. Lung transplantation and repair of complex congenital heart defects is possible; heart-lung transplantation may only be required for patients with severe left heart dysfunction and associated pulmonary vascular disease. Bronchiolitis obliterans remains a major concern for long-term graft function in pediatric lung transplant recipients.     

Evaluation of a pulsatile pediatric ventricular assist device in an acute right heart failure model

BACKGROUND: The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure. METHODS: Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. RESULTS: All results are expressed as mean +/- standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Base-line measurements were not significantly different between groups and included systemic arterial pressure, 80.6 +/- 12.7 mm Hg; right atrial pressure, 4.6 +/- 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 +/- 4.2 mm Hg; left atrial pressure, 4.8 +/- 0.8 mm Hg; and cardiac output, 1.4 +/- 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 +/- 10.4 mm Hg; right atrial pressure, 16.8 +/- 2.3 mm Hg; left atrial pressure, 1.4 +/- 0.5 mm Hg; and cardiac output, 0.6 +/- 0.1 L/min. All group 1 animals died at a mean of 71.4 +/- 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 +/- 13.0 mm Hg; right atrial pressure, 8.2 +/- 2.3 mm Hg; left atrial pressure, 6.4 +/- 2.1 mm Hg; and cardiac output, 1.0 +/- 0.2 L/min. CONCLUSIONS: The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.     

Effects of inhaled nitric oxide during permissive hypercapnia in acute respiratory failure in piglets

OBJECTIVE: To look for the effects of inhaled nitric oxide on oxygenation and pulmonary hemodynamics during acute hypercapnia in acute respiratory failure. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Ten piglets, weighing 9 to 13 kg. INTERVENTIONS: Acute respiratory failure was induced by oleic acid infusion and repeated lung lavages with 0.9% sodium chloride. The protocol consisted of three randomly assigned periods with different PaCO2 levels. Tidal volume was reduced to induce hypercapnia. Inspiratory time was prolonged to achieve similar mean airway pressures. During permissive hypercapnia, pH was not corrected. At each PaCO2 period, the animals were ventilated with inhaled nitric oxide of 10 parts per million and without nitric oxide inhalation. MEASUREMENTS AND MAIN RESULTS: Continuous hemodynamic monitoring included right atrial, mean pulmonary arterial, and mean systemic arterial pressures, arterial and mixed venous oxygen saturations, and continuous flow recording at the pulmonary artery. In addition, airway pressures, tidal volumes, dynamic lung compliance and airway resistance, end-tidal CO2 concentrations, and arterial and mixed venous blood gases were measured. Data were obtained at baseline and after lung injury, at normocapnia, at two levels of hypercapnia with and without nitric oxide inhalation. Acute hypercapnia resulted in a significant decrease in blood pH and a significant increase in mean pulmonary arterial pressure. There was no significant change in PaO2 during normocapnia and hypercapnia. Inhaled nitric oxide significantly decreased the mean pulmonary arterial pressure during both hypercapnic periods. It significantly improved oxygenation during both normocapnia and hypercapnia. CONCLUSIONS: Acute hypercapnia resulted in a significant increase in pulmonary arterial pressure without influencing oxygenation and cardiac output. Inhaled nitric oxide significantly reduced the pulmonary hypertension induced by acute permissive hypercapnia but did not influence the flow through the pulmonary artery. Inhaled nitric oxide significantly improved oxygenation in this model of acute lung injury during normocapnia and acute hypercapnia.     

The use of health care services by people with diabetes in rural areas

Stapled lung volume reduction surgery (LVRS) has recently been described for treatment of emphysema. Many questions arise regarding physiologic mechanisms of response from surgical treatment of emphysema. The objective of this study was to develop an animal model for the study of lung volume reduction surgery in diffuse heterogeneous emphysema. We hypothesized that elastic recoil would increase, static respiratory system compliance would decrease, and expiratory flows would increase after lung volume reduction surgery in animals with emphysema. In the study, emphysema was induced in 31 New Zealand White rabbits (3-5 kg) with endotracheally aerosalized porcine elastase (10,000-12,000 U). Lateral thoracotomies were performed 4-6 weeks postinduction under general anesthesia and mechanical ventilatory support. Stapled volume reduction was performed on the right lower lobe using a standard multirow pediatric stapler (U.S. Surgical). Pulmonary function tests were performed at baseline (preinduction), before stapling LVRS (postemphysema induction), immediately post stapling LVRS, and 1 week poststapling. Static respiratory system compliance, flow, conductance and forced expiratory flows, and peak flows at 20 and 40 cm3 of exhaled volume were analyzed. Animals were sacrificed 1 week poststapling, and bilateral lungs were harvested for histopathology. Diffuse but heterogeneous pulmonary emphysema was seen in these animals treated with high-dose aerosolized elastase. Static compliance increased, while expiratory flows and conductance decreased after induction of emphysema. Immediately post stapled volume reduction therapy, animals had decreased static compliance. By 1 week following surgery, animals showed increased forced expiratory flows and decreased expiratory resistance, although compliance was similar to preoperative levels. In conclusion, we describe initial results in an animal model of obstructive emphysema suitable for the study of lung volume reduction surgery. Changes in pulmonary function indicate that unilateral lower lobe LVRS increases airway conductance in the rabbits. Findings from LVRS studies in animal models such as this may help explain clinical improvement following LVRS in humans.     

Surfactant decreases pulmonary vascular resistance and increases pulmonary blood flow in the fetal lamb model of congenital diaphragmatic hernia

INTRODUCTION: Experiments using animal models of neonatal respiratory distress syndrome have shown a decrease in pulmonary vascular resistance (PVR) with surfactant replacement, whereas studies with the lamb model of congenital diaphragmatic hernia (CDH) have demonstrated improvement in oxygenation and lung mechanics with this therapy. The aim of the present study was to measure the effects of surfactant replacement therapy on the pulmonary hemodynamics of the lamb model of CDH. METHODS: Ten lambs with surgically created CDH and five control lambs were instrumented at term, with the placental circulation intact. Ultrasonic flow probes were positioned around the main pulmonary artery and the common origin of the left and right pulmonary arteries to record total lung and main pulmonary artery blood flow. Catheters were inserted to record systemic, pulmonary, and left atrial pressure. Five CDH animals received 50 mg/kg of surfactant by tracheal instillation just before delivery. All 15 animals were then ventilated for 4 hours. RESULTS: Correcting the surfactant deficiency in the CDH lamb resulted in a significant increase in pulmonary blood flow, a decrease in PVR, and a reduction in right-to-left shunting. These improvements in hemodynamics were associated with a significant improvement in gas exchange over 4 hours. CONCLUSION: The fetal lamb model of CDH has elevated PVR in comparison to controls. Prophylactic surfactant therapy reduces this resistance and dramatically increases pulmonary blood flow while reducing extrapulmonary shunt. A surfactant deficiency may be partially responsible for the persistent pulmonary hypertension in neonates with CDH.     

Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension

BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.     

Assessing risk by hemodynamic profile in patients awaiting cardiac transplantation

A profile of hemodynamic abnormalities in patients listed for cardiac transplantation was related to survival during the first year after listing. After a patient is listed for cardiac transplantation, the waiting period for a suitable donor heart is often long; therefore, objective criteria to determine risk would be helpful in identifying the group at highest risk of dying before receiving a transplant. Several studies have suggested certain hemodynamic parameters to be related to a poor prognosis. However, no 1 variable has emerged as an adequate predictor of survival in patients awaiting cardiac transplantation. One-year outcomes were examined in 138 consecutive patients listed for cardiac transplantation, who were grouped according to a hemodynamic risk score (HRS) based on abnormalities in baseline measures of right atrial pressure, pulmonary artery systolic pressure, transpulmonary gradient, cardiac output, cardiac index and pulmonary vascular resistance. Right atrial pressure alone was the most significant predictor of survival (p < 0.05). Patients with a right atrial pressure > 12 mm Hg had a 47% 1-year survival as compared with the 68% survival for those with a right atrial pressure < 12 mm Hg. HRS was the next strongest predictor of survival. The 66% survival in group I (HRS = 0) and the 69% survival in group II (HRS = 1 to 3) were significantly (p < 0.03) higher than the 41% survival in group III (HRS = 4 to 6) at 1 year after listing. Differences in survival for the HRS groups could not be explained by left ventricular ejection fraction, left ventricular end-diastolic diameter or status at listing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resection hip arthroplasty for malignant pelvic tumor. Outcome in 5 patients followed more than 2 years

BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some properties that provide protection from lung injury. Furthermore, its protective effect in cold storage of donor lungs has been confirmed. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution, and orthotopic left lung transplantations were performed. Rats were divided into four groups (n = 6). Group I received no preservation or storage. Groups II, III, and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP. Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial O2 tension values of groups III and IV were better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8, 373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3 +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01). Wet-dry weight ratio in group III was lower than in groups II and IV (group II, III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147, and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion injury in an in vivo rat lung transplantation model. Either administration of VIP via the flush solution or systemically just after reperfusion was associated with improved pulmonary function.     

County funding of mental health services in a rural state

A case of lobar torsion after lung surgery is reported here. She developed a right middle lobar torsion diagnosed by postoperative bronchial fiberscopy, suggesting incomplete obstruction of the intermedial bronchus. Re-operation was performed successfully either by fixing the right lower lobe to both the middle lobe and the thoracic wall. Careful postoperative observation with chest radiography, bronchial fiberscopy, are important for precise diagnosis of and therapy for lobar torsion following pulmonary lobectomy.     

Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of pulmonary metastases

BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin. METHODS: In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.     

Lung transplantation for Williams-Campbell syndrome

Williams-Campbell syndrome is a rare disorder characterized by a deficiency of cartilage in subsegmental bronchi leading to distal airway collapse and bronchiectasis. We report the first case of lung transplantation in a patient with end-stage lung disease secondary to Williams-Campbell syndrome. Although the patient did not have proximal airway collapse prior to transplantation, his posttransplant course was complicated by the development of bronchomalacia of the right and left mainstem bronchi. The patient experienced recurrent pulmonary infections and died of bacterial pneumonia 1 year after transplantation. Autopsy revealed cartilage deficiency in both right and left mainstem bronchi. A hypothesis may be made that a combination of proximal cartilage deficiency and posttransplant airway ischemia led to the development of bronchomalacia after lung transplantation. Thus, in contrast to previous reports, the cartilage deficiency in Williams-Campbell syndrome can involve both proximal and distal airways. Consequently, bilateral sequential lung transplantation may not be an effective therapeutic option in patients with this syndrome.     

Right ventricular function in orthotopic total atrioventricular heart transplantation

BACKGROUND: Total orthotopic heart transplantation was recently introduced into clinical practice as an alternative technique of orthotopic heart transplantation, adding bicaval and left and right pulmonary vein anastomoses to pulmonary artery and ascending aorta connection (total technique). The conventional technique (ventricular transplantation with atrioplasty) is compared with the total technique with particular emphasis on right ventricular performance. METHODS: Forty-eight mongrel dogs (23 to 31 kg) were used for 12 total and 12 standard orthotopic heart transplantations. Right ventricular (RV) function and atrial systole were analyzed with the use of micromanometry, sonomicrometry, and ultrasonic flow probes (preload-independent RV recruitable stroke work, RVPRSW). Fourier analysis was used to calculate RV power and pulmonary vascular impedance. RESULTS: There was no significant difference in cardiac ischemic and bypass times between the two groups. After transplantation, sinus rhythm was preserved after all total transplantations and after only one standard transplantation; no significant hemodynamic differences were observed. RVPRSW in the total group was conserved after transplantation; however, RVPRSW decreased by 39% (+/-8, p < .05) in the standard group. There was also a significant decrease in the rate of RV filling in the standard group after transplantation, suggesting decreased right atrial function. Pulmonary vascular impedance and RV power output were not significantly different after transplantation between the two groups. CONCLUSIONS: Total atrioventricular transplantation is a feasible alternative and conserves normal sinus rhythm. Ischemic and bypass times were not significantly different when the superior vena cava anastomosis is performed last after the release of the aortic cross-clamp. The insignificant decrease in the rate of RV filling with the use of the total technique suggests conserved RV diastolic function after transplantation with less decreased RV function in the total group.     

Congenital lobar emphysema resulting from bronchial sling around a normal right main pulmonary artery

A 5-month-old female infant was transferred to our institution for evaluation of recurrent upper respiratory tract symptoms and chest x-ray films showing hyperaeration of the right upper lobe. Preoperative studies including chest fluoroscopy, lung scan, and bronchoscopy suggested congenital lobar emphysema. At thoracotomy, an anomalous right upper lobe bronchus which bifurcated around the main pulmonary artery in a sling fashion was found. This anatomic abnormality has not been described previously and is a unique cause of congenital lobar emphysema.     

Assessment of cardiac filling pressure during continuous positive pressure ventilation

Before and after 10 dogs were near-drowned with fresh water, cardiac filling pressures were measured during spontaneous respiration, controlled mechanical ventilation with ambient expiratory airway pressure, continuous positive-pressure ventilation (CPPV) with 20 ml H2O PEEP, and CPPV alone. Pulmonary arterial occlusion and left ventricular end diastolic pressures were measured and compared. Intrapleural pressure was subtracted from values for each of these pressures to calculate respective transmural filling pressures. Mechanical ventilation and CPPV each decreased thoracic venous return, but only CPPV increased pulmonary arteriolar resistance. The increase of both airway pressure and pulmonary arteriolar resistance, in turn, increased both right atrial and pulmonary arterial occlusion pressures, but decreased left ventricular filling. Thus, measurement of pulmonary arterial occlusion pressure alone did not allow accurate assessment of cardiac filling pressure. The authors found that measurement of intrapleural pressure was necessary to obtain an accurate reflection of left ventricular filling pressure during CPPV. Momentary interruption of CPPV to measure any pressure was of no value in assessing vascular filling and caused pulmonary edema in several animals. Therefore, the authors recommend that vascular pressures be measured and evaluated without interruption of positive airway pressure.     

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.     

Bilateral Krukenberg tumors due to appendiceal mucinous carcinoid

Three cases of congenital polyalveolar lobe (pulmonary hamartoma) were diagnosed in female Thoroughbred foals. Foal 1 was born at full term but died shortly afterwards. Foal 2 was aborted at the seventh month of gestation. Parturition was induced at the tenth month of gestation in foal 3 because it developed hydrops of the amnion and ascites. In all three foals, the polyalveolar lobe occurred on the right side and affected the entire right lung. In each case, the right lung formed a tumour-like mass, and expanded into the left chest cavity. The lung masses were pink to dark red and spongy to rubbery, with marked lobular patterns on the pleural and cut surfaces. The left lung was compressed and small. The right and left lungs weighed 0.9-6.3 kg and 80 g-0.3 kg, respectively. Microscopically, the polyalveolar lobe consisted of normal alveoli, bronchioli and blood vessels, but the alveolus:artery ratio was greater than normal. In the polyalveolar lobe of two foals the numbers of alveoli per artery were 65.2 and 52.5; in contrast, the corresponding values for three control lungs were 26.9, 26.5 and 27.6. Chronic passive congestion with generalized oedema was observed in foals 2 and 3.     

The hemodynamic effects of the in-vivo administration of insulin-like growth-factor I

BACKGROUND: Recent studies have demonstrated that IGF-I has several biological activities that correlate with the GH axis, by acting as a cell protecting factor and a promoting compound in different tissues and organs. Our latest findings have demonstrated a potential application of IGF-I in the treatment of postischemic renal injury, which frequently appears after a kidney transplant. The beneficial effect of the renal postoperative recovery probably correlates with the regulation of the vascular tone, in which IGF-I plays a role with other cytokines. However, this rises the question whether IGF-I has any effect on the general hemodynamic status. This study was designed to underline the intraoperative hemodynamic effect of exogenous IGF-I in an experimental setting of renal transplantation in swine. METHODS: Twelve female swine underwent a left renal autotransplantation. At the reperfusion the animals were separated in two groups. Group one served as control. Group two received 400 micrograms of IGF-I (added to the flushing solution). The animals were kept under complete hemodynamic monitoring over the operation. RESULTS: Among the different parameters studied (mean arterial pressure, mean pulmonary arterial pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), any statistically significant difference between group one and two were observed. CONCLUSIONS: While the clinical administration of IGF-I requires further studies, the in vivo administration of this peptide is apparently well tolerated, and does not cause any hemodynamic instability to the operation.     

Thoracic surgery and liver dysfunction

Lung resection results in loss of lung parenchyma including residual healthy lung tissue and in reduction in pulmonary vascular bed. A decrease in residual pulmonary vascular bed after lung resection causes an increase in right heart afterload, and in some patients, it would be associated with an increase in right heart preload and consequent the changes in hepatic circulation which would lead to liver damage. Preceding thoracotomy, unilateral pulmonary arterial occlusion test (UPAO) was performed to simulate the hemodynamic changes after lung resection to evaluate the increase in right heart preload after surgery. Patients with the decreases in cardiac index or PaO2 during UPAO showed a higher levels of GPT during postoperative period when compared with those with the increase in either parameters. In a surgical treatment for empyema, bronchiectasis, or other infectious lung diseases, bronchial angiography (BAG) and also bronchial arterial embolization (BAE) were useful methods to prevent from exceeding bleeding during thoracotomy, which is one of the risk factors to cause liver damage after surgery. These results suggest that, in the field of thoracic surgery, the preoperative assessment of the hemodynamic changes caused by lung resection and the preoperative attempt to prevent from bleeding during thoracotomy are both important to protect from liver damage caused by surgical stress.